Project Summary: This is a competitive continuation application of a Training Program in the Molecular Biology of Cancer, which is in its 29th year of operation at the University of Virginia Health System. The last project period has seen a marked increase in the quality and cancer focus of the Training Faculty, a concomitant expansion in topical research choices for the students (particularly in epigenetics), a reorganization of recruiting and trainee selection methods, restructuring of the Cancer Training Grant (CTG) administration in response to these changes, the development of an Advanced Topics in Cancer course, an enhanced participation by trainees in cancer-related activities at the University of Virginia and in the surrounding community, and a greater emphasis on translational research. Thirty-three pre- and nine post-doctoral trainees were supported by this grant during the last funding period. Trainees have a wide variety of cancer-relevant research opportunities to choose from, including molecular genetics, molecular and cellular biology, biochemistry, membrane structure and function, structural biology, viral and bacterial oncology, immunology, signal transduction, development, differentiation, and drug discovery. The training program is multi-faceted, in-depth, and based on a Core Curriculum, independent research projects, and programmatic activities, such as formal courses on the Molecular Basis of Cancer and Advanced Topics in Cancer, Cancer Center seminars, an annual state-wide cancer symposium, clinical tumor boards at UVA hospital, and one-on-one encounters with cancer patients. The typical training period for pre-doctoral students is 5-6 years and for post-doctoral fellows, 4-8 years. However, financial support from the Cancer Training Grant is usually awarded for only two years of the training period. Ph.D. degrees or post-doctoral training can be obtained from any one of the seven participating departments or degree-granting programs, from whom the Training Faculty is chosen. New initiatives for the next grant period are proposed that will enhance programmatic activities (including community outreach), minority recruiting of post-doctoral fellows, and mechanisms of training program evaluation. Based on the previous success of this training program, as measured by the high percentage of past trainees who have chosen careers in cancer-related research and teaching activities, and the historical pre-doctoral emphasis of this CTG, support for 13 Ph.D. candidates and 4 post-doctoral trainees in each year is requested. Relevance: The goal of the Program is to prepare highly qualified individuals for careers in teaching and basic/ translational research relevant to problems in cancer biology. Through such research and teaching efforts, new approaches to preventing and treating cancers are anticipated.